The proposed research program will continue ongoing experimental studies on the fine structure of nerve fibers, focussing on the interrelation between the integrity of microtubules and the axonal transport of axoplasmic organelles (1). Concurrently, another line of research on developmental neuropathology will be started (2,3), with emphasis on experiments elucidating pathogenetic mechanisms involved in specific disease processes affecting infants: 1) Frog sciatic nerves are exposed in vitro to various compounds known or alleged to affect microtubules; microtubular damage is determined in electron micrographs by counts of tubules, neurofilaments and planimetry of axon profiles. These data are compared with electron microscopic and histochemical data on the extent of translocation of mitochondria in segments of nerves and their accumulation at nerve stumps. The goal of the study is to examine to what degree the morphologic integrity of the microtubular system is a prerequisite for the translocation of mitochondria. 2) In rats with experimentally indiced spina bifida and Arnold-Chiari deformity of the hindbrain, a systematic comparison will be done of the affectation of growth of neuroectodermal and mesodermal tissue structures by means of labelling with tritiated thymidine and determinations of DNA. The goal of the study is to determine whether there is any coordination, or lack thereof, in the development of neuroectodermal and mesodermal deformities in these diseases. 3) Pilot studies will be conducted for a series of experiments on the factors responsible for the affectation of certain nuclear groups in the brain in kernicterus.